Underivatized water-soluble .beta.(1-3)-glucan (also referred to as PGG-glucan or BETAFECTIN.RTM.) is a unique soluble .beta.-glucan which is prepared via a proprietary process. The biological activity of this polysaccharide differs from that of particulate or other soluble .beta.-glucans. Several laboratories have reported direct induction of arachidonic acid metabolites (Czop et al., J. Immunol. 141: 3170-3176 (1988)), cytokines (Abel and Czop, Intl. J. Immunopharmacol. 14: 1363-1373 (1992); Doita et al., J. Leuk. Biol. 14: 173-183 (1992)) and oxidative burst (Cain et al., Complement 4: 75-86 (1987); Gallin et al., Int. J. Immunopharmacol. 14: 173-183 (1992)) by both particulate and soluble forms of .beta.-glucans. In contrast, soluble .beta.(1-3)-glucan does not directly activate leukocyte functions such as oxidative burst activity (Mackin et al. FASEB J. 8:A216 (1994)), cytokine secretion (Putsiaka et al. Blood 82: 3695-3700 (1993)) or proliferation (Wakshull et al. J. Cell. Biochem. suppl. 18A: 22 (1994)). Instead, soluble .beta.(1-3)-glucan primes cells for activation by secondary stimuli (Mackin et al. (1994); Brunke-Reese and Mackin, FASEB J. 8: A488 (1994); and Wakshull et al. (1994)).
The biological activity of .beta.-glucans is mediated through specific receptors on target cells. Several investigators have described receptors which bind particulate .beta.-glucan preparations. For example, receptors for particulate .beta.-glucan (e.g., zymosan-like particles) have been described by Czop and colleagues (Czop and Kay, J. Exp. Med. 173: 1511-1520 (1991); Szabo et al., J. Biol. Chem. 270: 2145-2151 (1995)) and Goldman (Immunology 63 319-324 (1988); Exp. Cell Res. 174: 481-490 (1988)). The leukocyte complement receptor 3 (CR3, also known as MAC 1 or CD11b/CD18) has been shown to have the capacity to bind particulate and some soluble .beta.-glucans, as well as other polysaccharides (Thornton et al., J. Immunol. 156: 1235-1246 (1996)). A soluble aminated .beta.-glucan preparation has been shown to bind to murine peritoneal macrophages (Konopski et al., Biochim Biophys. Acta 1221: 61-65 (1994)), and a phosphorylated .beta.-glucan derivative has been reported to bind to monocyte cell lines (Muller et al., J. Immunol. 156: 3418-3425 (1996)). The ability of salmon macrophages (Engstad and Robertson, Dev. Comp. Immunol. 18: 397-408 (1994)) and brain microglial cells (Muller et al., Res. Immunol. 145: 267-275 (1994)) to phagocytose .beta.-glucan particles, presumably through a receptor-mediated process, has also been described.
Each of the foregoing studies utilized .beta.-glucan preparations varying widely in source, method of preparation, purity and degree of characterization. Because of this, little information is available regarding the relationship between .beta.-glucan structure/conformation and biological activity. There is, thus, a need for an improved understanding of .beta.-glucan structure/activity relationships to aid in the development of novel .beta.-glucan compositions with improved biological activity.